Cumulative Systolic Blood Pressure and Incident Stroke Type Variation by Race and Ethnicity

Key Points Question What is the association between cumulative systolic blood pressure (SBP) and incident stroke type, and do race and ethnicity modify this association? Findings In this cohort study using pooled data from 38 167 participants, higher cumulative SBP was associated with higher risk of overall stroke, ischemic stroke, and intracerebral hemorrhage but not subarachnoid hemorrhage. Although the risk of incident stroke type varied by race and ethnicity, little evidence suggested that race and ethnicity modified the association between cumulative SBP and incident stroke type. Meaning These findings suggest that clinicians should emphasize SBP control as a means of stroke prevention regardless of patient race or ethnicity.


Introduction
High blood pressure (BP) is a major modifiable risk factor for all 3 major stroke types: ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH).Over the past decade, guidelines for the standard of care and evaluation of BP have been updated, reclassifying hypertension guidelines. 1 In 2017, BP guidelines were updated, redefining systolic BP (SBP) with the following measures, based on a mean of at least 2 careful readings obtained on at least 2 occasions: less than 120 mm Hg indicates normal; 120 to 129 mm Hg, elevated or prehypertension; 130 to 139 mm Hg, stage 1 hypertension; and 140 mm Hg or greater, stage 2 hypertension. 2,3The reclassification of SBP levels also provides additional insight for physicians and patients on differential levels of elevated cardiovascular risk. 1 Previous research has shown that using the mean of multiple SBP measurements over time, long-term cumulative mean SBP has a greater predictive value than single SBP measurements [4][5][6] and tends to provide better estimations of major cardiovascular events and BP control than traditional BP measures.However, the association between cumulative mean SBP and incident stroke type (IS, ICH, and SAH) is unclear.
The prevalence of hypertension and stroke is higher in Black adults than White adults in the US, likely the result of public health and health care inequities. 7Less clear is whether the association between cumulative SBP and incident stroke type differs by racial and ethnic group.One study 8 found that elevated baseline SBP was associated with a higher stroke risk among Black participants than White participants; however, ischemic and hemorrhagic strokes were combined.Conversely, another study found the association between baseline hypertension (defined as a BP measurement Ն160/95 mm Hg or self-reported history of hypertension or antihypertensive drug use) and IS did not differ among Black, Caribbean Hispanic, and White participants. 9e objective of our study was to clarify the association between cumulative mean SBP and incident stroke types (IS, ICH, and SAH) and explore how race and ethnicity affect these associations.
We hypothesized that race and ethnicity would modify the association between cumulative mean SBP and incident stroke type-specifically, that the magnitude of the association between cumulative mean SBP and stroke incidence (overall and by stroke type) would be greater in Black participants than in White participants.1][12][13] Dates covered across the 6 studies ranged from January 1, 1971, to December 31, 2019.5][16] Participants were included in the analysis if they were 18 years or older at cohort baseline, had an SBP measurement at cohort baseline, had at least 1 cohort study visit after baseline, and self-reported as Black race, Hispanic of any race, or White race.

Study Design and Participants
Participants with a history of prevalent stroke at cohort baseline were excluded. 5This study was approved by the University of Michigan Institutional Review Board.The cohort studies were approved by participating institutions, and participants provided written informed consent.This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Outcomes
Our primary time-to-event outcome was time from the baseline visit to the first incident stroke.
Secondary outcomes included time to first incident IS, ICH, and SAH, regardless of whether the patient has experienced other stroke types before.Each cohort measured incident strokes during follow-up using similar protocols.8][19][20][21][22] Stroke events were defined as "rapidly developing clinical signs of focal, at times global, disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin." 23r fatal strokes, the medical history, hospital records, interviews with next of kin or proxies, and death certificate or National Death Index data were reviewed to adjudicate the cause of death.
Experts further classified strokes as IS, ICH, or SAH; CHS included SAH in the ICH category, so CHS was omitted from SAH models..

Measurement of Race and Ethnicity
Study participants self-reported their race and ethnicity in 1 of 3 groups: Black, Hispanic of any race, or White.The study incorporated the social construct of racial and ethnic categories to reflect general social definitions that are shaped by complex historical processes in the US. 24Including race and ethnicity in the analysis provides an opportunity to use empirical research to discuss how future interventions could address and help narrow the current inequitable gaps in stroke treatment and care among different racial and ethnic groups. 25By study design, ARIC, CARDIA, CHS, MESA, and NOMAS recruited Black and White participants, whereas MESA and NOMAS also recruited Hispanic participants.The CHS had a small number of self-reported Hispanic participants of any race (n = 59).
Participants in the FOS were included because they provide geographic and age diversity and contribute information and precision for the estimates of time to stroke type in White participants and the estimates of stroke risk associated with SBP.

Measurement of BP
1][12][13] We calculated the time-dependent cumulative mean of all SBPs (ie, a time-varying running mean) updated to reflect each SBP measurement before the event.

Covariates
Sociodemographic covariates included age, gender, sex, educational level, and cohort study.Vascular risk factors included current cigarette smoking, physical activity, body mass index, waist circumference, history of atrial fibrillation, fasting glucose level, low-density lipoprotein cholesterol level, alcohol use, and time-dependent antihypertensive medication use.Participants with no antihypertensive medication use recorded at all visits were considered nonusers.All covariates except for antihypertensive medication use were measured at baseline.

Statistical Analysis Main Analysis
Data were analyzed from January 1, 2022, to January 2, 2024.A subgroup analysis approach using Kaplan-Meier methods and log-rank tests for overall stroke and stroke type were used to evaluate the cumulative incidence of first event and compare curves stratified by the 3 race and ethnicity groups. 26,27We constructed multivariable Cox proportional hazards models to test the association between time-dependent cumulative mean SBP and the time-to-event outcomes adjusting for covariates.Racial and ethnicity differences in the association between SBP and stroke or stroke type were examined by (1) including an SBP by race and ethnicity interaction term in the model, and (2)   stratifying analyses of SBP by racial or ethnic stratum and reported using hazard ratios (HRs).We used multiple imputations (10 imputed datasets) to replace the missing covariates at baseline. 28,29zard ratios are shown for a 10-mm Hg increase in cumulative mean SBP.Analyses were performed Statistical significance for all analyses was set as 2-sided P < .05.

Sensitivity Analysis
To examine whether the observed differences in SBP-related stroke risk (HRs) by race and ethnicity were due to cohort variation, we separated the cohorts into 2 groups and repeated the analyses within the 2 groups separately.The first group included cohorts that did not recruit Hispanic participants by design (ARIC, CARDIA, CHS, and FOS, excluding the 59 Hispanic participants in CHS).
The second group included cohorts that recruited Hispanic participants by study design (MESA and NOMAS).Further details are provided in the eTable in Supplement 1.

Results
The

Absolute Risks for Overall Stroke and Stroke Type
Among the 3 stroke types, the proportion remaining free of incident stroke type was higher among participants who experienced SAH and ICH compared with those who experienced IS. Figure 2 presents the Kaplan-Meier survival curves for time to incident stroke type.

Association of SBP With Overall Stroke and Stroke Type
Figure 3 shows the HRs of cumulative mean SBP for the incidence of overall stroke and stroke subtypes adjusted for covariates: 3502 participants had a stroke, 2952 had an IS, 448 had an ICH, and 98 had an SAH.A 10-mm Hg higher cumulative mean SBP was associated with a 20% higher risk of overall stroke (HR, 1.20 [95% CI, 1.18-1.23]),20% higher risk of IS (HR, 1.20 [95% CI, 1.17-1.22]),and 31% higher risk of ICH (HR, 1.31 [95% CI, 1.25-1.38]).The 13% higher risk of SAH associated with a 10-mm Hg higher cumulative mean SBP was not significant (HR, 1.13 [95% CI, 0.99-1.29];P = .06).HRs can be found in the eFigure in Supplement 1).

Exploring Whether Race and Ethnicity Modifies the Association Between SBP and Stroke
When all 6 cohorts were examined, race and ethnicity did not modify the association between cumulative mean SBP and risk of IS (race/ethnicity × SBP interaction term, P = .85)or SAH (race/ ethnicity × SBP interaction term, P = .89)but did modify the association for ICH (race/ethnicity × SBP interaction term, P = .02)(eTable in Supplement 1).An analysis restricted to the 4 cohorts that recruited Black and White participants by design (n = 28 849) similarly suggested that race did not

Strengths and Limitations
Our study has several strengths.We used data collected across the US to widen our findings' generalizability by pooling data from 6 population cohort studies that have diversity in age, geographic diversity, and race and/or ethnicity.Two advantages of a pooled cohort analysis include the increased study power to examine effect modification and the ability to examine risks across large samples of participants with heterogeneous exposures. 43r study also has potential limitations.Although we adjusted for educational level, we did not include other socioeconomic factors that could be potential confounders, such as income, because they were unavailable for all cohorts at or before the first incidence of stroke. 44,45Although our study examines a broad age range of participants, our study examined participants' age at baseline only.
We did not investigate the influence of age on the associations among cumulative mean SBP, race and ethnicity, and incident stroke risk.Future research should examine the effect of age on the association between cumulative mean SBP and stroke risk among diverse populations, as advanced age has been identified as a risk factor for stroke incidence.The number of cases with SAH was small, limiting the ability to detect an association with cumulative mean SBP.

Conclusions
In this cohort study of 38 167 participants, our study results have clinical and research implications.
Our results suggest that cumulative mean SBP was a potent modifiable risk factor for stroke, IS, and ICH.However, since 2007 to 2008, BP control has not improved and has worsened. 468][49] Although selfmonitoring of BP improves BP control and is cost-effective, it is an underused tool, and cost is a barrier, making patient education and greater insurance coverage priorities. 50,51Although we found no clear evidence that the association between SBP on incident stroke type differed by race and ethnicity, stroke risk varied by race and ethnicity, with Black participants having higher IS and ICH risk and Hispanic participants having higher ICH risk than White participants. 39,52Examining racial inequities advances our understanding of the social, economic, and political structures that affect health behaviors, experiences, and incident stroke for racial and ethnic minority groups. 24Our findings highlight the importance of providing culturally informed stroke prevention programs addressing modifiable risk factors such as BP, along with social determinants of health and structural inequities in society.

Figure 2 .Figure 3 .
Figure 2. Absolute Risks for Overall Stroke and Stroke Type This pooled cohort analysis used individual participant data from 6 US prospective cohort studies with repeated measures of BP: the Atherosclerosis Risk in Communities Study (ARIC), Coronary Artery Risk Development in Young Adults Study (CARDIA), Cardiovascular Health Study (CHS), Cumulative Systolic Blood Pressure and Incident Stroke Type by Race and Ethnicity JAMA Network Open.2024;7(5):e248502.doi:10.1001/jamanetworkopen.2024.8502(Reprinted) May 3, 2024 3/12 Downloaded from jamanetwork.comby guest on 05/05/2024 using SAS, version 9.4 (SAS Institute Inc) and R, version 4.1.1(R Project for Statistical Computing).

Table .
Baseline Characteristics and Stroke Incidence Among Participants HR, 1.51 [95% CI, 0.86-2.66).Compared with White participants, Hispanic participants of any race had a 281% higher risk of SAH (HR, 3.81 [95% CI, 1.29-11.22]),but not other stroke types.Kaplan-Meier survival curves for time to incident stroke type by race and ethnicity representing unadjusted a Unless otherwise indicated, data are expressed as No. (%) of participants with available data.b d Includes participants with available data.e Calculated as weight in kilograms divided by height in meters squared.fOne drink equals approximately 14 grams of alcohol in our harmonized variable based on a self-report of alcohol use.( MESA and NOMAS differ from those in the other 4 cohorts.Alternatively, it is possible that the statistical power for testing interactions was much smaller in the subgroup analysis of MESA and NOMAS than in the subgroup analysis of the 4 cohorts (ARIC, CARDIA, CHS, and FOS), which featured a larger sample size.
Models for overall stroke, ischemic stroke (IS), and intracerebral hemorrhage (ICH) used multivariable adjusted Cox proportional hazard regression.HR indicates hazard ratio; SAH, subarachnoid hemorrhage; SBP, systolic blood pressure.in